Evidence map›Paper›PMID 25532759›Full record

ArticleThe pharmacogenomics journal2015

Distinct gene expression profiles of proximal and distal colorectal cancer: implications for cytotoxic and targeted therapy.

M K H Maus, D L Hanna, C L Stephens, S H Astrow, D Yang, P P Grimminger, F Loupakis, J H Hsiang, G Zeger, T Wakatsuki and 2 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The pharmacogenomics journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.8field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 45 citations in OpenAlex.

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  13. IntegratingWorld journal of gastroenterology · 2017
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 2 countries.

M K H Maus1] Department of General, Visceral and Tumor Surgery, University of Cologne, Cologne, Germany [2] Response Genetics, Inc., Los Angeles, CA, USA.
D L HannaDivision of Medical Oncology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
C L StephensResponse Genetics, Inc., Los Angeles, CA, USA.
S H AstrowResponse Genetics, Inc., Los Angeles, CA, USA.
D YangDivision of Medical Oncology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
P P GrimmingerDepartment of General, Visceral and Tumor Surgery, University of Cologne, Cologne, Germany.
F Loupakis1] Division of Medical Oncology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA [2] Oncologia Medica, Azienda Ospedaliero-Universitaria Pisana, Instituto Toscano, Tumori, Italy.
J H HsiangResponse Genetics, Inc., Los Angeles, CA, USA.
G Zeger1] Response Genetics, Inc., Los Angeles, CA, USA [2] Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
T WakatsukiDivision of Medical Oncology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
A BarziDivision of Medical Oncology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
H-J LenzDivision of Medical Oncology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
University of Southern California · USUniversity of Cologne · DE

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MYLES G COCKBURN · 1985 to 2026
$181.4M
NCI NIH HHS P30 CA014089NCI NIH HHS P30CA014089-27S1
6 · The paper itself

Abstract

Colorectal cancer (CRC) is a heterogeneous disease with genetic profiles and clinical outcomes dependent on the anatomic location of the primary tumor. How location has an impact on the molecular makeup of a tumor and how prognostic and predictive biomarkers differ between proximal versus distal colon cancers is not well established. We investigated the associations between tumor location, KRAS and BRAF mutation status, and the messenger RNA (mRNA) expression of proteins involved in major signaling pathways, including tumor growth (epidermal growth factor receptor (EGFR)), angiogenesis (vascular endothelial growth factor receptor 2 (VEGFR2)), DNA repair (excision repair cross complement group 1 (ERCC1)) and fluoropyrimidine metabolism (thymidylate synthase (TS)). Formalin-fixed paraffin-embedded tumor specimens from 431 advanced CRC patients were analyzed. The presence of seven different KRAS base substitutions and the BRAF V600E mutation was determined. ERCC1, TS, EGFR and VEGFR2 mRNA expression levels were detected by reverse transcriptase-PCR. BRAF mutations were significantly more common in the proximal colon (P<0.001), whereas KRAS mutations occurred at similar frequencies throughout the colorectum. Rectal cancers had significantly higher ERCC1 and VEGFR2 mRNA levels compared with distal and proximal colon tumors (P=0.001), and increased TS levels compared with distal colon cancers (P=0.02). Mutant KRAS status was associated with lower ERCC1, TS, EGFR and VEGFR2 gene expression in multivariate analysis. In a subgroup analysis, this association remained significant for all genes in the proximal colon and for VEGFR2 expression in rectal cancers. The mRNA expression patterns of predictive and prognostic biomarkers, as well as associations with KRAS and BRAF mutation status depend on primary tumor location. Prospective studies are warranted to confirm these findings and determine the underlying mechanisms.

Indexed as

AdultAgedAged, 80 and overAntineoplastic AgentsBiomarkers, TumorColonic NeoplasmsColorectal NeoplasmsDNA-Binding ProteinsDrug Delivery SystemsEndonucleasesErbB ReceptorsFemaleGene Expression ProfilingHumansMaleMiddle AgedAntineoplastic AgentsBiomarkers, TumorBRAF protein, humanDNA-Binding ProteinsEGFR protein, humanEndonucleasesErbB ReceptorsERCC1 protein, humanKDR protein, humanKRAS protein, humanProto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)RNA, MessengerVascular Endothelial Growth Factor Receptor-2

Identifiers

PMID25532759
PMCPMC4478287
OpenAlexW2044305358

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.